Formulation and optimization of leflunomide-loaded NLC-gel for improved skin permeation and anti-inflammatory...

Arthritis is a chronic-inflammatory disorder that impairs joint function and necessitates efficient localised treatment. This research aimed to formulate and optimise leflunomide-loaded nanostructured lipid carriers (NLCs) for topical delivery. Dynasan 114 and corn oil were used as the solid and liquid lipids, respectively, and NLCs were formulated using high-speed homogenisation and probe sonication. Dual experimental design (1) Plackett-Burman for screening, and (2) Box-Behnken for formulation optimisation were employed. The optimised NLCs showed particle size (125.5 nm), PDI (0.188), zeta potential (-15.5 mV), and entrapment efficiency (92.20 ± 1.28%). FT-IR, DSC, P-XRD, and TEM validated the amorphous dispersion of leflunomide within the lipid matrix and the spherical morphology of the NLCs. The optimised NLCs were integrated into a Carbopol 980 NF (0.75%) gel base, demonstrating appropriate rheological properties such as extrudability (176 g), adhesiveness (-112 g), and pH (6.92). The gel formulation demonstrated prolonged drug release (96% over 24 h) and increased ex-vivo permeation with flux of 0.3632 mg/cm²/hour, hence validating enhanced diffusion through the skin barrier. The in-vivo pharmacodynamic study using a carrageenan-induced paw edoema model exhibited an 89.40% reduction in inflammation, exceeding the efficacy of the marketed leflunomide formulation. These findings suggest that the leflunomide-loaded NLC-based gel offers a promising platform for dermal drug distribution and enhanced anti-inflammatory activity.